The objective of this application is to understand the molecular mechanisms involved in the hormonal regulation and tissue-specific expression of the GnRHR gene. The specific aims include 1) determine the physiologic regulation of GnRHR gene transcription and mRNA stability in vivo and in vitro by GnRH, activin, and estrogen; 2) identify and characterize functional cis-DNA elements of the mouse GnRHR gene and identify factors which interact with these elements; 3) identify and characterize cis-DNA elements and factors that mediate GnRH responsiveness; 4) use the 5'-flanking region of the GnRHR gene to direct oncogene expression to the pituitary in an attempt to develop LH- and FSH-producing cell lines; and 5) use GnRHR transgenes to study the regulation by GnRH, activin, and steroid hormones.